Chronic alcoholic liver disease affects millions of individuals worldwide and is a major cause of liver transplantation and death. Although the majority will not develop complications, 15-40% may develop serious liver sequelae, including end-stage liver disease and hepatocellular carcinoma. Those at the highest risk include patients with cirrhosis and alcoholic steato-hepatitis (Mathurin P, et al. J Hepatol. 2002; 36:480-7).
Alcoholic steato-hepatitis (ASH) is a necrotizing inflammatory lesion that in its severe form (severe ASH) is associated with high mortality despite corticosteroids treatment (Mathurin P, et al. Gastroenterology. 1996; 110:1847-53; Mathurin P, et al. J Hepatol. 2002; 36:480-7).
Non-alcoholic steato-hepatitis (NASH) is a necrotizing inflammatory lesion that in its severe form is associated with serious liver sequelae, including end stage liver disease and hepatocellular carcinoma (Angulo P. N. Engl. J. Med. 2002 Apr. 18; 346(16):1221-31). NASH is the severe form of liver steatosis associated with diabetes, overweight, hyperlipemia, arterial hypertension and hyperuricemia (Angulo P. N. Engl. J. Med. 2002 Apr. 18; 346(16):1221-31).
Current guidelines for the diagnosis of ASH or NASH recommend to use the AST/ALT ratio in non-severe patients (Angulo P. N. Engl. J. Med. 2002 Apr. 18; 346(16):1221-31; Maher J J. Semin Gastrointest Dis. 2002; 13:31-9) and the liver biopsy in severe patients with the Maddrey discriminant function above 32 (Levitsky J, Mailliard M E. Semin Liver Dis. 2004; 24:233-47; Mathurin P, et al. Gastroenterology. 1996; 110:1847-53; Mathurin P, et al. J Hepatol. 2002; 36:480-7). As liver biopsy is still an invasive and costly procedure, with a potential sampling error, it could be advantageous to have a fast and easy to perform test that would give a good predictive value of the level of ASH or NASH in the patient.
Several studies have observed that some serum biomarkers of fibrosis had better diagnostic values than the standard serum markers of necrosis as transaminases or ActiTest (Naveau S, et al. Clin Gastroenterol Hepatol. 2005; 3(2); Castera L, et al. J Hepatol. 2000; 32:412-8; Annoni G, et al. Hepatology. 1989; 9:693-7; Nojgaard C, et al. J Hepatol. 2003; 39:179-86; Chossegros P. 1995; 22(2 Suppl):96-9), but none of these studies has really identified an accurate combination of markers of ASH.
For the diagnosis of liver fibrosis and/or presence of liver necroinflammatory lesions, non-invasive FibroTest (FT) (Biopredictive, Paris France, U.S. Pat. No. 6,631,330) has been validated as surrogate marker in chronic hepatitis C (Poynard T, et al. Comp Hepatol. 2004; 3:8) and B (Myers R P, et al. J Hepatol. 2003; 39:222-30) and recently in alcoholic liver disease (Callewaert N, et al. Nature Med 2004; 10; 1-6; Naveau S, et al. Clin Gastroenterol Hepatol. 2005; 3(2)).
However, no such diagnosis test is currently available for the more precise diagnosis of ASH or NASH. There is therefore a need to develop a diagnosis method that would give a good predictive value of the presence or the absence of ASH or NASH in a patient, and that would be reliable enough to reduce the need of liver biopsy. This method would be particularly advantageous for a patient suffering from a disease involving alcoholic or non-alcoholic steato-hepatitis, for instance with heavy alcohol consumption, or who already had a positive diagnostic test of liver fibrosis or necroinflammatory lesions, to adapt the treatment to his precise disease.